Biology subjects

Paredes, M.

Publications and source records attributed to Paredes, M..

11 recordsLinked to original sources

bioRxiv2026

Overlapping flower and pollen production in two imperiled pitcher plants raises conservation challenges

Balancing sexual reproduction with vegetative growth poses challenges for many plants. Additionally, reproductive effort, such as production of pollen or flowers, is not always correlated with numbers of viable and germinable seeds. Energetic tradeoffs like these can be particularly fraught for imperiled species and might be especially complicated in landscapes with a possibility of interspecific hybridization. In this multi-year study, we track the reproductive effort, flowering phenology, and reproductive output of two interfertile Sarracenia (pitcher plants). We show that reproductive effort varies among years and sites, and that production of pollen and flowers does not always result in higher seed output. We demonstrate that phenological overlap in the timing of flower production and pollen viability could enable hybridization, and that the more imperiled taxon produces fewer seeds per flower. Results have implications for conservation of these pitcher plants, management of hybridization in these and other systems, and general principles of reproductive allocation.

ecology↗

bioRxiv2026

A multimodal interrogation of Broca's area in the pediatric and adult human brain

Language is a defining trait of our species, and disruptions in language acquisition can have profound consequences to the individuals affected. Uncovering the neurodevelopmental basis of this complex trait requires detailed molecular and cellular insights into the neocortical areas that support linguistic abilities. Here we performed joint gene expression and chromatin accessibility profiling at single-nucleus resolution (10x Genomics Single cell Multiome) and spatial transcriptomic profiling (Xenium high-plex in situ spatial transcriptomics) of Brocas area alongside adjacent motor cortical areas. We profiled individuals from different ancestries (European and African) and developmental stages (infancy, childhood, adolescence, and adulthood). We provide a high-resolution dissection of the cellular and molecular architecture of Brocas and motor cortical areas across early life stages and anchor the trajectories to the cellular states found in the adult human brain. We identify distinct area- and stage-specific cellular signatures, including a prominent role of glia populations and interneuron subtypes contributing to cytoarchitectonic specializations. Using longitudinal single cell spatial transcriptomic profiling, we orthogonally validate our consensus cell taxonomy and spatially resolve layer enrichment of neuronal and astrocyte subtypes that distinguish Brocas area and motor cortex. We also uncover cell type-specific molecular signatures that distinguish cell developmental trajectories in these cortical areas, including an early molecular code established by differential expression of cadherin genes that might contribute to area-specific intercellular communication. We also identify cell type-specific vulnerabilities to language- related neurodevelopmental and neuropsychiatric disorders, with selective susceptibility of particular somatostatin-positive interneuron subtypes to ASD/ADHD. Finally, evolutionary analysis of differentially accessible regions between Brocas area and motor cortex suggests that genetic mutations that might have contributed to the emergence of linguistic abilities accumulated over the course of million years following the divergence of human and chimpanzee lineages. Together, our study provides a comprehensive molecular, cellular and spatial definition of Brocas area and motor cortex, laying the groundwork for investigations into unique aspects of human cognition and related neurodevelopmental and neuropsychiatric disorders.

neuroscience↗

bioRxiv2026

Multiphasic myelination and dendritic growth modulate qMRI signals in human visual cortex.

How does myelin develop in human visual cortex? By combining immunohistochemistry with in vivo and postmortem magnetic resonance imaging of longitudinal relaxation rate (R1), which increases with myelin content, we find that myelin and R1 increase across development but follow distinct trajectories. Immunohistochemistry reveals two phases of myelination: an infant phase of limited oligodendrogenesis, with myelin restricted to deep cortical layers, followed by widespread myelination across all layers during childhood. Cortical R1 also increases across development and correlates with myelin by childhood. However, in infancy, R1 increases outpace myelin growth and instead tracks dendritic arborization, indicating that the microstructural drivers of R1 change across development. We hypothesize that deep layer myelination in infancy contributes to early visual function whereas later myelination of superficial layers enables prolonged cortical plasticity and learning of complex visual behaviors.

neuroscience↗

bioRxiv2024

Microglia regulate GABAergic neurogenesis in prenatal human brain through IGF1

GABAergic neurons are an essential cellular component of neural circuits. Their abundance and diversity have enlarged significantly in the human brain, contributing to the expanded cognitive capacity of humans. However, the developmental mechanism of the extended production of GABAergic neurons in the human brain remains elusive. Here, we use single-cell transcriptomics, bioinformatics, and histological analyses to uncover microglial regulation of the sustained proliferation of GABAergic progenitors and neuroblasts in the human medial ganglionic eminence (hMGE). We show that insulin-like growth factor 1 (IGF1) and its receptor IGR1R as the top ligand-receptor pair underlying microglia-progenitor communication in the prenatal human brain. Using our newly developed neuroimmune hMGE organoids, which mimics hMGE cytoarchitecture and developmental trajectory, we demonstrate that microglia-derived IGF1 promotes progenitor proliferation and the production of GABAergic neurons. Conversely, IGF1-neutralizing antibodies and IGF1 knockout human embryonic stem cells (hESC)-induced microglia (iMG) completely abolished iMG-mediated progenitor proliferation. Together, these findings reveal a previously unappreciated role of microglia-derived IGF1 in promoting proliferation of neural progenitors and the development of GABAergic neurons.

neuroscience↗

bioRxiv2024

Conservation, alteration, and redistribution of mammalian striatal interneurons

Mammalian brains vary in size, structure, and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved1-4. Recent studies suggest there is a primate-specific population of striatal inhibitory interneurons, the TAC3 interneurons5. However, there has not yet been a detailed analysis of the spatial and phylogenetic distribution of this population. Here, we profile single cell gene expression in the developing pig (an ungulate) and ferret (a carnivore), representing 94 million years divergence from primates, and assign newborn inhibitory neurons to initial classes first specified during development6. We find that the initial class of TAC3 interneurons represents an ancestral striatal population that is also deployed towards the cortex in pig and ferret. In adult mouse, we uncover a rare population expressing Tac2, the ortholog of TAC3, in ventromedial striatum, prompting a reexamination of developing mouse striatal interneuron initial classes by targeted enrichment of their precursors. We conclude that the TAC3 interneuron initial class is conserved across Boreoeutherian mammals, with the mouse population representing Th striatal interneurons, a subset of which expresses Tac2. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development.

evolutionary biology↗

bioRxiv2024

Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex. We solve the structure of the seipin/Adig complex by Cryo-EM at 2.98[A] overall resolution. Surprisingly, seipin can form two unique oligomers, undecamers and dodecamers. Adig selectively binds to the dodecameric seipin complex. We further find that Adig promotes seipin assembly by stabilizing and bridging adjacent seipin subunits. Functionally, Adig plays a key role in generating lipid droplets in adipocytes. In mice, inducible overexpression of Adig in adipocytes substantially increases fat mass, with enlarged lipid droplets. It also elevates thermogenesis during cold exposure. In contrast, inducible adipocyte-specific Adig knockout mice manifest aberrant lipid droplet formation in brown adipose tissues and impaired cold tolerance.

cell biology↗

bioRxiv2023

Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy

STRUCTURED ABSTRACTO_ST_ABSIntroductionC_ST_ABSMosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathological finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. MethodsWe present a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA-sequencing (snRNA-seq) of brain tissue from the second resection. ResultssnRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. DiscussionsnRNA-seq may be used to infer the cell type-specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

neuroscience↗

bioRxiv2022

Single-cell analysis of prenatal and postnatal human cortical development

We analyze more than 700,000 single-nucleus RNA-seq profiles from 106 donors during prenatal and postnatal developmental stages and identify lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineate enhancer-gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identify the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs upregulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development. One Sentence SummarySingle-cell transcriptomic atlas of human cortical development identifies lineage and sex-specific programs and their implication in brain disorders.

neuroscience↗

bioRxiv2022

A CRISPR-engineered Isogenic Model Reveals Altered Neuronal Phenotypes of the 22q11.2 A-B Syndromic Deletion

The 22q11.2 deletion syndrome (22q11.2DS), associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided important insight into the mechanisms of phenotypic features of this condition. However, patient-derived iPS models may harbor underlying genetic heterogeneity that can confound analysis of pathogenic CNV effects. Furthermore, the [~]1.5 Mb "A-B" deletion at this locus is inherited at higher frequency than the more common [~]3 Mb "A-D" deletion, but remains under-studied due to lack of relevant models. To address these issues, here we leveraged a CRISPR-based strategy in Cas9-expressing iPS cells to engineer novel isogenic models of the 22q11.2 "A-B" deletion. After in vitro differentiation to excitatory neurons, integrated transcriptomic and cell surface proteomics identified deletion-associated alterations in surface adhesion and cell signaling. Furthermore, implantation of iPS-derived neuronal progenitor cells into the cortex of neonatal mice found accelerated neuronal maturation within a relevant microenvironment. Taken together, our results suggest pathogenic mechanisms of the 22q11.2 "A-B" deletion in driving neuronal and neurodevelopmental phenotypes, both in vitro and in vivo. We further propose that the isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.

genetics↗

bioRxiv2021

Molecular diversity and lineage commitment of human interneuron progenitors

Cortical interneurons are indispensable for proper function of neocortical circuits. Changes in interneuron development and function are implicated in human disorders, such as autism spectrum disorder and epilepsy. In order to understand human-specific features of cortical development as well as the origins of neurodevelopmental disorders it is crucial to identify the molecular programs underlying human interneuron development and subtype specification. Recent studies have explored gene expression programs underlying mouse interneuron specification and maturation. We applied single-cell RNA sequencing to samples of second trimester human ganglionic eminence and developing cortex to identify molecularly defined subtypes of human interneuron progenitors and immature interneurons. In addition, we integrated this data from the developing human ganglionic eminences and neocortex with single-nucleus RNA-seq of adult cortical interneurons in order to elucidate dynamic molecular changes associated with commitment of progenitors and immature interneurons to mature interneuron subtypes. By comparing our data with published mouse single-cell genomic data, we discover a number of divergent gene expression programs that distinguish human interneuron progenitors from mouse. Moreover, we find that a number of transcription factors expressed during prenatal development become restricted to adult interneuron subtypes in the human but not the mouse, and these adult interneurons express species- and lineage-specific cell adhesion and synaptic genes. Therefore, our study highlights that despite the similarity of main principles of cortical interneuron development and lineage commitment between mouse and human, human interneuron genesis and subtype specification is guided by species-specific gene programs, contributing to human-specific features of cortical inhibitory interneurons.

neuroscience↗

bioRxiv2018

Antimicrobial, Antioxidant and Anti-Inflammatory Activities of Proteins of Phaseoulus lunatus (Fabaceae) Baby Lima Beans Produced in Ecuador

Phaseoulus lunatus L., a variety of baby lima bean, which is produced in the coastal region of Ecuador, is a profitable crop of that country. Various cultivars of this common bean are considered a sources for nutraceutical compounds, such as bioactive peptides. To assess the potential biologic activities of protein isolates and hydrolysates of P. lunatus baby lima beans, this study evaluates the proteins antimicrobial, antioxidant and anti-inflammatory activities. Antioxidant activity was measured by the TBARS method. In-vitro anti-inflammatory activity was measured by the inhibition of denatured protein as well as a diffusion method, according with CLSI guidelines by antimicrobial activity. Both fractions (isolate and hydrolysates) showed anti-inflammatory and antioxidant activity. However, protein hydrolysates (pH 5) had a better performance than protein isolates. The same effect was observed in antimicrobial activity, when protein hydrolysates had a broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria. These preliminary studies suggest that P. lunatus baby lima beans could have a considerable biological activity for nutraceutical applications.

microbiology↗